tbuckley/cabot-search huggingface dataset:
Target‐Catalyzed Self‐Assembly of DNA‐Streptavidin Nanogel for Enzyme‐Free miRNA Assay
Authors: Jae Chul Park, Hyebin Na, Saehan Choi, Huiju Jeon, Yoon Sung Nam
Journal: Advanced Healthcare Materials (2022)

Rapid, sensitive, specific, and user-friendly microRNA (miRNA) assays are in high demand for point-of-care diagnosis. Target-catalyzed toehold-mediated strand displacement (TMSD) has received increasing attention as an enzyme-free molecular tool for DNA detection. However, the application of TMSD to miRNA targets is challenging because relatively weak DNA/RNA hybridization leads to failure in the subtle kinetic control of multiple hybridization steps. Here, a simple method is presented for miRNA assay based on the one-pot self-assembly of Y-shaped DNAs with streptavidin via an miRNA-catalyzed TMSD cascade reaction. A single miRNA catalyzes the opening cycle of DNA hairpin loops to generate multiple Y-shaped DNAs carrying biotin and a quencher at the end of their arms. Introducing a single base-pair mismatch near the toehold facilitates RNA-triggered strand displacement while barely disturbing nonspecific reactions. The Y-shaped DNAs are self-assembled with fluorescently labeled streptavidin (sAv), which produces nanoscale DNA-sAv nanogel particles mediating efficient Förster resonance energy transfer in their 3D network. The enhancing effect dramatically reduces the detection limit from the nanomolar level to the picomolar level. This work proves that TMSD-based DNA nanogel with a base-pair mismatch incorporated to a hairpin structure is a promising approach towards sensitive and accurate miRNA assay.
90 K increased delivery efficiency of extracellular vesicles through mediating internalization
Authors: Guiquan Zhu, Fan Yang, Hongxuan Wei, Wanrong Meng, Jianguo Gan, Linlin Wang, Chuanshi He, Shun Lu, Bangrong Cao, Huaichao Luo, Bo Han, Ling Li
Journal: Journal of Controlled Release (2022)
Prospects for hypoxia-based drug delivery platforms for the elimination of advanced metastatic tumors: From 3D modeling to clinical concepts
Authors: Mohammad Shahpouri, Mohammad Amin Adili-Aghdam, Hossein Mahmudi, Mehdi Jaymand, Zohreh Amoozgar, Mohsen Akbari, Michael R. Hamblin, Rana Jahanban-Esfahlan
Journal: Journal of Controlled Release (2022)
TIGIT blockade repolarizes AML-associated TIGIT<sup>+</sup>M2 macrophages to an M1 phenotype and increases CD47-mediated phagocytosis
Authors: Franziska Brauneck, Brit Fischer, Marius Witt, Jana Muschhammer, Jennyfer Oelrich, Pedro Henrique da Costa Avelar, Sophia Tsoka, Lars Bullinger, Elisa Seubert, Daniel J Smit, Carsten Bokemeyer, Christin Ackermann, Jasmin Wellbrock, Friedrich Haag, Walter Fiedler
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Leukemia-associated macrophages (LAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype, function, and plasticity of these cells. The present study provides an extensive characterization of macrophages in patients with acute myeloid leukemia (AML). Methods The phenotype and expression of coregulatory markers were assessed on bone marrow (BM)-derived LAM populations, using multiparametric flow cytometry. BM and blood aspirates were obtained from patients with newly diagnosed acute myeloid leukemia (pAML, n=59), patients in long-term remission (lrAML, n=8), patients with relapsed acute myeloid leukemia (rAML, n=7) and monocyte-derived macrophages of the blood from healthy donors (HD, n=17). LAM subpopulations were correlated with clinical parameters. Using a blocking anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody or mouse IgG2α isotype control, we investigated polarization, secretion of cytokines, and phagocytosis on LAMs and healthy monocyte-derived macrophages in vitro. Results In pAML and rAML, M1 LAMs were reduced and the predominant macrophage population consisted of immunosuppressive M2 LAMs defined by expression of CD163, CD204, CD206, and CD86. M2 LAMs in active AML highly expressed inhibitory receptors such as TIGIT, T-cell immunoglobulin and mucin-domain containing-3 protein (TIM-3), and lymphocyte-activation gene 3 (LAG-3). High expression of CD163 was associated with a poor overall survival (OS). In addition, increased frequencies of TIGIT + M2 LAMs were associated with an intermediate or adverse risk according to the European Leukemia Network criteria and the FLT3 ITD mutation. In vitro blockade of TIGIT shifted the polarization of primary LAMs or peripheral blood-derived M2 macrophages toward the M1 phenotype and increased secretion of M1-associated cytokines and chemokines. Moreover, the blockade of TIGIT augmented the anti-CD47-mediated phagocytosis of AML cell lines and primary AML cells. Conclusion Our findings suggest that immunosuppressive TIGIT + M2 LAMs can be redirected into an efficient effector population that may be of direct clinical relevance in the near future.
In Situ Structure Transformation of a Sprayed Gel for pH‐Ultrasensitive Nano‐Catalytic Antibacterial Therapy
Authors: Zhihui Niu, Mingxiao Xie, Zicheng Wei, Yang Guo, Mengxuan Han, Yingying Ding, Jianyu Huang, Kang Zheng, Yao Zhang, Yuanda Song, Dechao Niu, Yongsheng Li, Guangwu Wen, Xiaowei Li, Jianlin Shi
Journal: Advanced Healthcare Materials (2022)

Abstract Nano‐catalytic bacterial killing provides new opportunities to address ever‐increasing antibiotic resistance. However, the intrinsic catalytic activity usually depends on a much lower pH conditions (pH = 2–5) than that in the weakly acidic bacterial microenvironments (pH = 6–7) for reactive oxygen species production by Fenton reactions. Herein, a MnSiO 3 ‐based pH‐ultrasensitive “in situ structure transformation” is first reported to significantly promote the adhesion between material and bacteria, and shorten the diffusion distance (&lt;20 nm) to compensate ultra‐short life (&lt;200 ns) of ·OH generated by Mn 2+ ‐mediated Fenton‐like reaction, finally enhancing its nano‐catalytic antibacterial performance in weakly acidic conditions. A separated spray bottle is further designed to achieve in situ gelation at the wound site, which demonstrates excellent shape adaptability to complicated and rough surfaces of wounds, allowing for long‐term nano‐catalyst release. As a result, bacterial‐infected wound healing is efficiently promoted. Herein, the in situ sprayed nano‐catalytic antibacterial gel presents a promising paradigm for bacterial infection treatment.
Metabolic enzyme LDHA activates Rac1 GTPase as a noncanonical mechanism to promote cancer
Authors: Juan Liu, Cen Zhang, Tianliang Zhang, Chun-Yuan Chang, Jianming Wang, Ludvinna Bazile, Lanjing Zhang, Bruce G. Haffty, Wenwei Hu, Zhaohui Feng
Journal: Nature Metabolism (2022)
Introduction of General Chapters on standard methods for allergen quantification in the European Pharmacopoeia
Authors: Julia Zimmer, Andreas Bonertz, Susanne Kaul, Stefan Vieths
Journal: Allergy (2022)

Abstract The Biological Standardization Project BSP090 has been successfully concluded in 2021. As a result, two standard methods for quantification of the major allergens Bet v 1 and Phl p 5 will be implemented in the European Pharmacopoeia (Ph. Eur.). The General Chapter describing the protocol of the respective Bet v 1‐specific ELISA has already been adopted by the Ph. Eur. Commission and will become an official part of the Ph. Eur. in the beginning of 2023. As this will be the first allergen‐specific standard method in the EU, this paper intends to summarize the preceding process and outline the measures necessary to comply with the new regulatory requirement.
Projections of Type 1 and Type 2 Diabetes Burden in the U.S. Population Aged &amp;lt;20 Years Through 2060: The SEARCH for Diabetes in Youth Study
Authors: Thaddäus Tönnies, Ralph Brinks, Scott Isom, Dana Dabelea, Jasmin Divers, Elizabeth J. Mayer-Davis, Jean M. Lawrence, Catherine Pihoker, Lawrence Dolan, Angela D. Liese, Sharon H. Saydah, Ralph B. D’Agostino, Annika Hoyer, Giuseppina Imperatore
Journal: Diabetes Care (2022)

OBJECTIVE To project the prevalence and number of youths with diabetes and trends in racial and ethnic disparities in the U.S. through 2060. RESEARCH DESIGN AND METHODS Based on a mathematical model and data from the SEARCH for Diabetes in Youth study for calendar years 2002–2017, we projected the future prevalence of type 1 and type 2 diabetes among youth aged &amp;lt;20 years while considering different scenarios of future trends in incidence. RESULTS The number of youths with diabetes will increase from 213,000 (95% CI 209,000; 218,000) (type 1 diabetes 185,000, type 2 diabetes 28,000) in 2017 to 239,000 (95% CI 209,000; 282,000) (type 1 diabetes 191,000, type 2 diabetes 48,000) in 2060 if the incidence remains constant as observed in 2017. Corresponding relative increases were 3% (95% CI −9%; 21%) for type 1 diabetes and 69% (95% CI 43%; 109%) for type 2 diabetes. Assuming that increasing trends in incidence observed between 2002 and 2017 continue, the projected number of youths with diabetes will be 526,000 (95% CI 335,000; 893,000) (type 1 diabetes 306,000, type 2 diabetes 220,000). Corresponding relative increases would be 65% (95% CI 12%; 158%) for type 1 diabetes and 673% (95% CI 362%; 1,341%) for type 2 diabetes. In both scenarios, substantial widening of racial and ethnic disparities in type 2 diabetes prevalence are expected, with the highest prevalence among non-Hispanic Black youth. CONCLUSIONS The number of youths with diabetes in the U.S. is likely to substantially increase in future decades, which emphasizes the need for prevention to attenuate this trend.
Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using <scp>Genome‐Wide</scp> Imputation
Authors: Simon Rothwell, Christopher I. Amos, Frederick W. Miller, Lisa G. Rider, Ingrid E. Lundberg, Peter K. Gregersen, Jiri Vencovsky, Neil McHugh, Vidya Limaye, Albert Selva‐O'Callaghan, Michael G. Hanna, Pedro M. Machado, Lauren M. Pachman, Ann M. Reed, Øyvind Molberg, Olivier Benveniste, Pernille Mathiesen, Timothy Radstake, Andrea Doria, Jan L. De Bleecker, Boel De Paepe, Britta Maurer, William E. Ollier, Leonid Padyukov, Terrance P. O'Hanlon, Annette Lee, Lucy R. Wedderburn, Hector Chinoy, Janine A. Lamb
Journal: Arthritis & Rheumatology (2022)

Objective The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed variants from the ImmunoChip array using a large reference panel to fine‐map associations and identify novel associations in IIM. Methods We analyzed 2,565 Caucasian IIM patient samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically matched control samples. We imputed 1,648,116 variants from the ImmunoChip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM and clinical and serologic subgroups. Results The HLA locus was consistently the most significantly associated region. Four non‐HLA regions reached genome‐wide significance, SDK2 and LINC00924 (both novel) and STAT4 in the whole IIM cohort, with evidence of independent variants in STAT4 , and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases ( TEC and LTBR ). We identified more significant associations than those previously reported in IIM for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A ‐ BLK loci in PM, and for CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells. Conclusion We found novel and strong associations in IIM and PM and localized signals to single genes and immune cell types.
Methodological Issues in Study of Daily Insulin Dose and Cancer Risk Among Patients With Type 1 Diabetes—Reply
Authors: Yuanjie Mao, Wenjun Zhong
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Methodological Issues in Study of Daily Insulin Dose and Cancer Risk Among Patients With Type 1 Diabetes
Authors: Rachel G. Miller, Tina Costacou
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Prediction of Erosive Disease Development by Antimitochondrial Antibodies in Rheumatoid Arthritis
Authors: Richard E. Moore, Ting Wang, Bhargavi Duvvuri, Marie L. Feser, Kevin D. Deane, Joshua J. Solomon, J. Lee Nelson, M. Kristen Demoruelle, Christian Lood
Journal: Arthritis & Rheumatology (2022)

Objective Mitochondria are found in the extracellular space in rheumatoid arthritis (RA). However, whether mitochondria are a source of autoantigens in RA has not been carefully addressed. Thus, we undertook this study to investigate the presence and significance of antimitochondrial antibodies (AMAs) in patients with RA. Methods AMAs were measured in serum samples from 3 cross‐sectional cohorts of RA patients (n = 95, n = 192, and n = 117) and healthy individuals (n = 38, n = 72, and n = 50) using a flow cytometry–based assay. Further, AMAs were detected using an anti–mitofusin‐1 (anti–MFN‐1) IgG enzyme‐linked immunosorbent assay and Western blot analysis. A longitudinal inception cohort, followed up for a median of 8 years, was used to study disease progression. Results AMA levels were elevated in RA patients from all 3 cohorts as compared to healthy individuals ( P &lt; 0.001, P &lt; 0.05, and P &lt; 0.01), with a range of 14–26% positivity. Levels of anti–MFN‐1 antibodies correlated with AMA levels (r = 0.31, P = 0.006) and were elevated in RA patients as compared to healthy individuals ( P &lt; 0.001). The presence of AMAs was associated with erosive disease ( P &lt; 0.05) and interstitial lung disease ( P &lt; 0.01). Further, AMA levels were found to predict erosive disease (odds ratio [OR] 4.59, P = 0.006) and joint space narrowing (OR 3.08, P = 0.02) independent of anti–citrullinated protein antibodies. Finally, anti–MFN‐1 antibodies identified seronegative patients developing erosive disease (OR 9.33; P = 0.02). Conclusion Our findings demonstrate the presence of novel autoantibodies targeting mitochondria in the setting of RA. AMAs were used to stratify patients based on disease phenotype and to predict development of erosive disease, including in patients with seronegative disease. Our results highlight the essential role of mitochondria in the pathogenesis of RA and suggest a possible benefit of therapies targeting mitochondrial‐mediated inflammation and clearance in these patients.
Independent Evolution of Sex Chromosomes and Male Pregnancy–Related Genes in Two Seahorse Species
Authors: Xin Long, Deborah Charlesworth, Jianfei Qi, Ruiqiong Wu, Meiling Chen, Zongji Wang, Luohao Xu, Honggao Fu, Xueping Zhang, Xinxin Chen, Libin He, Leyun Zheng, Zhen Huang, Qi Zhou
Journal: Molecular Biology and Evolution (2022)

Unlike birds and mammals, many teleosts have homomorphic sex chromosomes, and changes in the chromosome carrying the sex-determining locus, termed "turnovers", are common. Recent turnovers allow studies of several interesting questions. One question is whether the new sex-determining regions evolve to become completely non-recombining, and if so, how and why. Another is whether (as predicted) evolutionary changes that benefit one sex accumulate in the newly sex-linked region. To study these questions, we analyzed the genome sequences of two seahorse species of the Syngnathidae, a fish group in which many species evolved a unique structure, the male brood pouch. We find that both seahorse species have XY sex chromosome systems, but their sex chromosome pairs are not homologs, implying that at least one turnover event has occurred. The Y-linked regions occupy 63.9% and 95.1% of the entire sex chromosome of the two species and do not exhibit extensive sequence divergence with their X-linked homologs. We find evidence for occasional recombination between the extant sex chromosomes that may account for their homomorphism. We argue that these Y-linked regions did not evolve by recombination suppression after the turnover, but by the ancestral nature of the low crossover rates in these chromosome regions. With such an ancestral crossover landscape, a turnover can instantly create an extensive Y-linked region. Finally, we test for adaptive evolution of male pouch-related genes after they became Y-linked in the seahorse.
Colonic drug delivery: Formulating the next generation of colon-targeted therapeutics
Authors: Laura E. McCoubrey, Alessia Favaron, Atheer Awad, Mine Orlu, Simon Gaisford, Abdul W. Basit
Journal: Journal of Controlled Release (2022)

Colonic drug delivery can facilitate access to unique therapeutic targets and has the potential to enhance drug bioavailability whilst reducing off-target effects. Delivering drugs to the colon requires considered formulation development, as both oral and rectal dosage forms can encounter challenges if the colon's distinct physiological environment is not appreciated. As the therapeutic opportunities surrounding colonic drug delivery multiply, the success of novel pharmaceuticals lies in their design. This review provides a modern insight into the key parameters determining the effective design and development of colon-targeted medicines. Influential physiological features governing the release, dissolution, stability, and absorption of drugs in the colon are first discussed, followed by an overview of the most reliable colon-targeted formulation strategies. Finally, the most appropriate in vitro, in vivo, and in silico preclinical investigations are presented, with the goal of inspiring strategic development of new colon-targeted therapeutics.
Two-Year Follow-up From the T1GER Study: Continued Off-Therapy Metabolic Improvements in Children and Young Adults With New-Onset T1D Treated With Golimumab and Characterization of Responders
Authors: Mark R. Rigby, Beverly Hayes, Yinglei Li, Frank Vercruysse, Joseph A. Hedrick, Teresa Quattrin
Journal: Diabetes Care (2022)

The T1GER (A Study of SIMPONI to Arrest β-Cell Loss in Type 1 Diabetes) study showed many metabolic benefits of the tumor necrosis factor-α blocker golimumab in children and young adults with type 1 diabetes (T1D). Off-therapy effects are reported.T1GER was a phase 2, placebo-controlled, randomized trial in which golimumab or placebo was administered for 52 weeks to participants 6-21 years old diagnosed with T1D within 100 days of randomization. Assessments occurred during the 52-week on-therapy and 52-week off-therapy periods.After treatment was stopped, C-peptide area under the curve (AUC) remained greater in the treatment versus control group. At weeks 78 and 104, the golimumab group had lower reductions in the 4-h C-peptide AUC baseline than the placebo group, where specifically the golimumab group had reductions of 0.31 and 0.41 nmol/L, and the placebo group had reductions of 0.64 and 0.74 nmol/L. There were also trends in less insulin use, higher peak C-peptide levels and those in partial remission, and higher peak C-peptide levels in the golimumab group. Golimumab responders, defined as having an increase or minimal loss of C-peptide AUC and/or being in partial remission at week 52, showed even greater improvements in most metabolic parameters on and off therapy and had less hypoglycemia during the off-therapy period versus placebo. Adverse events, including infections, were similar between the groups during all time periods of the study.In children and young adults with new-onset T1D, golimumab preserved endogenous β-cell function and resulted in other favorable metabolic parameters on and off therapy. A subpopulation had disease stabilization while on therapy, with improved metabolic parameters off therapy.
The therapeutic and commercial landscape of stem cell vesicles in regenerative dermatology
Authors: O.G. Davies, S. Williams, K. Goldie
Journal: Journal of Controlled Release (2022)

Extracellular vesicles (EVs) are lipid enveloped nanoparticles that are naturally produced by cells and function in the intercellular transfer of biological material such as proteins, RNAs and metabolites. They have been shown to act in an autocrine and paracrine manner to alter the functions of local and distant recipient cells, with a growing body of evidence highlighting their wide-ranging functions in regenerative processes such as stem cell maintenance, tissue repair and immune modulation. EVs offer several potential advantages over stem cell therapies such as improved safety profiles, scalability, and enhanced storage and quality control of the final product. In fact, many of the pro-regenerative outcomes of stem cell therapies have been attributed to the release of mesenchymal stem cell-derived EVs (MSC-EVs) and their potent effects on extracellular matrix turnover, local cell recruitment, proliferation and angiogenesis is now well described. These positive outcomes have led to clinical trials assessing the safety of MSC-EVs for applications in wound healing and the treatment of cutaneous ulcers, as well as the emergence of multiple commercial MSC-EV sources marketed for topical application in cosmetic medicine. However, regenerative EV therapeutics remain in their infancy and pertinent questions regarding product standardisation, potency and the regulatory landscape surrounding the development of these promising nano-therapeutics must be addressed to ensure safe and effective clinical adoption. In this article we provide an overview of the emerging landscape of MSC-EVs in regenerative dermatology and cosmetic science, highlighting the underlying biological mechanisms pertinent to their application and providing a perspective on current safety considerations, regulation and future directions in the field.